Research Summaries

VIDO-InterVac will be one of the largest Containment Level 3 vaccine research and development facilities in North America. Following are summaries of some of the research already being conducted at VIDO, in the researchers’ own words.

Prion Diseases: Drs. Scott Napper, Andy Potter and Philip Griebel
Prion diseases or transmissible spongiform encephalopathies (TSEs) are a family of progressive neurodegenerative disorders that affect both humans and animals. VIDO is researching how natural prions develop into disease-causing forms and how those infectious prions cause diseases. In particular, VIDO is developing a TSE vaccine for ruminants as an effective strategy to control or eradicate prion diseases in both domestic and wild animal populations. This vaccine is centred around a specific epitope that has been identified and optimized as a highly attractive target immunotherapeutic intervention. The sequence of the targeted region is conserved across species and the vaccine under development has potential application in preventing and/or treating CWD. Working with fellow collaborators Dr. Neil Cashman (University of British Columbia) and Dr. Lorne Babiuk (University of Alberta), VIDO is conducting vaccine challenge trials in sheep and mice. These trials will help determine whether the epitope has sufficient immunogenicity to induce protective responses, so that the vaccine can block or treat infection.

A number of diseases such as Alzheimers, Parkinson’s and ALS are also protein folding disorders. Similar immunotherapy approaches that target the immune responses against the epitopes exposed in the misfolded areas hold similar promise for control and/or treatment.
Influenza: Dr. Yan Zhou
The influenza project at VIDO was launched in May, 2005 with a long-term goal of finding effective ways to control and prevent influenza epidemics and pandemics. With funding provided by provincial, federal and international agencies, VIDO has been studying cellular mechanisms to identify the specific pathways used by influenza A viruses during viral replication and propagation in cells. We’ve also established a reverse genetic system for Canadian swine influenza A virus (H1N1) and have generated mutant viruses that can be used as live vaccines for swine influenza infection.

Vaccination is the primary method for the prevention of influenza disease and live vaccines are thought to offer better protection than their inactivated counterparts. As part of this, one of our research goals is to generate a live attenuated vaccine for swine-origin H1N1 virus in pigs. Dr. Zhou and VIDO have established both national and international collaborations in conjunction with the National Pandemic Preparedness Programs.
E. coli and Food Safety: Dr Andy Potter
The work of graduate student David Asper on E. coli O157 and its “cousins” represents a significant advance in our knowledge about how this group of organisms is able to colonize cattle and suggests strategies that might be employed for the development of intervention methods on the farm. E. coli O157 uses a unique mechanism to attach to cells in the gastrointestinal tract of cattle and humans and this has been the basis for the development of a first generation vaccine for cattle. However, this first generation vaccine only provides protection against E. coli serotype O157 and not others. The non-O157 types of E. coli are becoming more of a problem on a global basis and in some countries (e.g. Argentina), other types can be the dominant organism associated with human disease.

Potter’s research demonstrated which bacterial components from all Shigatoxin-producing E. coli strains (O157, etc.) were recognized by the immune systems of both cattle and humans, laying a foundation for the development of a vaccine for cattle that will protect against all types. From a basic research perspective, this is significant, but it also has very clear ramifications for commercial vaccine development. At the present time, E. coli O157 is classified as a CL2 pathogen in North America but there has been movement towards increased biocontainment requirements. In some parts of the world, it is already classified as a CL3 pathogen and we anticipate that the International Vaccine Centre facility will be required for this type of work in the future.
Hepatitis C: Drs. Sylvia van den Hurk, Qiang Liu and Joyce Wilson
Hepatitis C virus is an important human pathogen, which affects an estimated 170 million people worldwide. Most HCV infections become chronic and can proceed to fatty liver, liver cirrhosis or hepatocellular carcinoma. HCV infections are the leading cause of liver transplants in North America. Chronic HCV infections are presently treated with interferon and ribavirin, which are expensive, often come with serious side effects and are successful in only about half of treated patients. VIDO researchers are examining the hepatitis C virus from 3 angles:
  • Dr. Sylvia van den Hurk is studying the effects of the HCV on human dendritic cells, the cells which are pivotal to development of immune response. HCV impairs these cells by adversely affecting their ability to function and mature. Using immunomodulatory compounds, Dr. van den Hurk is seeking ways to boost the immune response of dendritic cells in individuals with chronic HCV.
  • Dr. Wilson is studying how HCV engages miRNA to promote its own growth, and is experimenting with novel strategies that can inhibit virus replication.
  • Cells normally use their cellular microRNA (miRNA) to suppress translation and viral growth, the hepatitis C virus is able to bypass this. Dr. Liu is studying the molecular mechanisms by which HCV causes steatosis, which is abnormal fat retention in the liver. Their research goals include determining whether steatosis causes liver failure and development of effective therapeutics to prevent or retard steatosis.

When InterVac is completed, research involving Hepatitis C can be accelerated as CL3 facilities are required for more extensive studies of the virus.
Immune Modulation: Dr. George Mutwiri
Research pertaining to immune modulation is a relatively new field in the medical treatment of infectious disease, and a field that complements all vaccine research activities. With immune modulation, vaccine formulations for both CL2 and CL3 organisms can be modified with immunostimulatory agents or alternative delivery systems, thereby boosting specific areas of the body’s immune system, making the body more effective at fighting off infection.
  • Much of Dr. Mutwiri’s research is centered on the discovery that specific DNA sequences, referred to as CpGs, can stimulate innate immune responses. His group is developing immunostimulatory CpG oligodeoxynucleotide (ODN) for use as therapeutic compounds for poultry, cattle and swine and as components of animal vaccines.
  • His group is also studying synthetic biodegradable water-soluble polymers as potential platforms for formulating and delivering animal and human vaccines. Polymers can magnify the intensity and stability of immune responses and research has shown they are effective adjuvants in small animals (sheep, pigs) and do not cause tissue reactions at injection sites. Dr. Mutwiri is also investigating the adjuvant activity and delivery potential in large animal species, the mechanism which mediates adjuvant activity of these polymers and their potential to form microparticles and nanoparticles for mucosal delivery of vaccines and immune activators.
  • A recent collaboration coupled Dr. Mutwiri’s expertise in polyphosphazenes with a company that had developed a modified skin patch for vaccine delivery. Skin patches with microneedles coated with polyphosphazene immunoadjuvant and antigen were successfully tested for intradermal immunization. This technology offers ease of immunization and dose sparing potential for situations where vaccine supplies are limited.
Neonatal Mucosal Immunology: Dr. Philip Griebel
Mucosal surfaces provide the largest interface between our bodies and the external environment and as such, is the primary route for the introduction and entry of infectious agents. The mucosal immune system must balance the preventing of infection with the maintenance of key biological functions, and this balancing act is the hard to achieve during the neonatal period.

In September, 2009, Dr. Philip Griebel was appointed as the new Canada Research Chair in Neonatal Mucosal Immunology. With this prestigious appointment, Dr. Griebel is establishing a seven-year research program that will identify mucosal vaccine strategies against viral and bacterial enteric infections that are established during the neonatal period. This research will involve a broad group of VIDO researchers, VIDO graduate students and external collaborators. As an example, graduate student Patrick Fries is developing methods to isolate and identify dendritic cells from the small intestine - dendritic cells function as key communicators between the epithelial barrier and the immune system. Graduate student Mehran Yarahmadi is investigating interactions between dendritic cells and neutrophils.

This research will include the mucosal immune system for both the upper respiratory tract and the intestine, with an ultimate goal of preventing entry of infectious agents and significantly changing neonatal health management. We will study immune responses during both acute and chronic infections. Chronic infection experiments may require two to three years to complete and the capacity to isolate animals within the VIDO-InterVac CL3 facilities is critical. The findings will benefit both animal and human health.